Biomedical subjects
Publications and source records attributed to C Greco.
In a 74-year old female, admitted to the Acute Stroke Unit for a cerebral reversible ischemic attack, we investigated the occurrence of ischemic alterations on ECG, recorded during an acute relapse, using 99mTc (MIBI) myocardial scintigraphy. Scintigrams showed a transient anteroseptal and inferior hypoperfusion. This is the first direct demonstration of myocardial ischemia occurring during stroke.
Sufficient evidence exists today pointing to the relationship between high levels of plasma cholesterol and coronary atherosclerosis. Up to now, however, the last criterion for validating the aetiopathogenetic relationship between dyslipidemia and CHD, i.e., the demonstration that reduction of plasma cholesterol reduced the formation or progression of the plaque and the incidence of its fatal or non-fatal cardiac and vascular complications, has been lacking. For more than two decades, numerous trials have had this aim in mind but until very recently results have not been substantiated owing to various deficiencies in the method. Before publication of the NHLBI Task Force of Atherosclerosis, eleven major randomised clinical studies based on hypolipidemia interventions were completed. The three studies involving dietetic interventions were considered non-conclusive overall because of the lack of a double-blind factor and of other important epidemiological criteria. Of three pharmacological trials only two involved studies of primary prevention carried out on a population of hypercholesterolaemics. These produced partial results on certain cardiac end-points but not on total deaths and at times not even on deaths from CHD. Multifactorial studies, finally, were even less demonstrative. Taken together, however, the trials based on hypolipidemia interventions point to interesting though not definitive evidence of a reduction in blood cholesterol levels to reduce the incidence and mortality from CHD. According to the NHLBI, many of these studies lacked important features that were codified and suggested for later studies.(ABSTRACT TRUNCATED AT 250 WORDS)
The cytotoxic effect of the combination of N-methylformamide (NMF) with 5-fluorouracil (5-FU) on cell survival of the human colon cancer line HT29 was assessed. The differentiating activity of NMF was evidenced by morphological maturation and conversion of cell culture characteristics to those consistent with a more benign phenotype. In combination experiments, the noncytotoxic concentration of 1% NMF was chosen and doses of 5-FU ranging from 5 to 25 micrograms/ml were employed. Two main schedules were tested either on exponentially or stationarily growing cells: (a) 1% NMF for 72 h followed by 12-h exposure to 5-FU; (b) 5-FU for 12 h followed by 72-h exposure to 1% NMF. The results obtained demonstrated that the 5-FU----NMF sequence determined a powerful reduction in the surviving fraction of HT29 cells, while the reverse sequence did not increase the killing effect of 5-FU given alone. Immunocytochemical and scanning electron microscopy studies seemed to confirm that the association in which the differentiating agent followed the 5-FU treatment strongly impaired cellular integrity and function and that cytoskeletal elements, particularly microfilaments, and surface structures could play an essential role in the mechanisms of cytotoxicity. Furthermore, the results of this work indicate that drug sequence is a critical factor for the optimal combination of 5-FU and NMF.
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We report the first published case (to our knowledge) of histopathologically documented acquired immunodeficiency syndrome-related cytomegalovirus (CMV) myelitis in which antiviral drug therapy was administered. Despite sensitivity of the patient's CMV isolate to therapy with both ganciclovir and foscarnet, use of neither of these agents halted progression of central nervous system CMV disease. Higher doses of these drugs or combination therapy may be required to treat acquired immunodeficiency syndrome-related CMV myelitis effectively.
Two continuous human glioma derived cell lines, LI and DF, were established in our laboratory. Both cell lines showed cytological features and in vitro behavior similar to those of the respective original neoplasms. These two lines were characterized for their main biological properties including in vitro and in vivo growth rate, clonogenic ability and tumorigenicity in nude mice. The plating efficiencies were generally high both during exponential and stationary growth phases and a high tumorigenicity was observed. All injected nude mice developed tumors. The two lines were tested for chemosensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cis-Diamminedichloroplatinum II (DDP). Heterogeneity in biological features and in drug sensitivity was observed. Exposure of the two lines to BCNU and DDP showed that the glioblastoma (LI) was less sensitive than the anaplastic astrocytoma (DF). For both lines BCNU was more effective on cells in plateau than in exponential phase, while the killing effect of DDP was not phase-dependent.
We report the occurrence of erroneous discharge from an implanted automatic cardioverter/defibrillator during transesophageal atrial pacing. Transesophageal pacing was performed as part of a study protocol on the inducibility of ventricular tachycardia from the atrium in patients with ischemic heart disease. At an induced heart rate of 166 beats per minute (a value just above the cut-off rate of the device), the cardioverter/defibrillator was triggered. This observation suggests that transesophageal atrial pacing could be utilized to disclose the potential for spurious discharges in the event of fast atrial rhythms in patients with the automatic implantable cardioverter/defibrillator.
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Lonidamine (LND), an indazole-carboxylic acid derivative, was delivered alone and together with adriamycin (ADM) or hyperthermia to the human melanoma cell line M14, and cell survival was assessed. Cell cycle-specific effects were investigated by analyzing sequences of DNA content histograms by means of a suitable mathematical procedure. LND delivered for 1 h at a dose of 50 micrograms/ml did not affect proliferation and survival of the cells. Exposure of the cells for 1 h to ADM (1.0 microgram/ml) followed by LND for 1 h (50 micrograms/ml) produced the highest effect on the survival. Kinetic parameters were affected by the combined treatment slightly more than by ADM exposure alone. Simultaneous delivery of LND (50 micrograms/ml) with hyperthermia (42 degrees C, 1 h) reduced the survival and enhanced the block of cells in the G2M phase, as compared with the heat treatment alone. The effect of the treatments on cell survival appeared to be related to the perturbation of the G2M phase of the cycle.
The human melanoma cell line M14 has been proven in previous experiments to be much less sensitive to the action of heat (42 degrees C, 60 min) than other melanoma lines. In the present study, we have investigated the possibility of increasing the effect of heat by means of drug treatment. Thermochemotherapy was applied to exponentially growing cells according to different schedulings, and was analyzed in its efficacy by measuring the impairment of the cellular colony-forming ability. Findings of the present study point out that: (a) appropriate sequencing between hyperthermia and cis-diamminedichloroplatinum II(DDP), melphalan (L-Pam), 1,2,4-dichlorobenzyl-1H-indazol-3-carboxylic acid (LNA) or 5-3,3-dimethyl-1-triazeno-imidazole-4-carboxamide (DTIC) strongly influences the cytotoxic effect of the two agents; and (b) the optimal combination appears to be the simultaneous application of heat and drugs. However, as far as thermochemotherapy with DDP is concerned, a synergistic effect may also be achieved when hyperthermia precedes DDP.
Cardiovascular anomalies are found in 50% of the cases of Turner's and Noonan's syndromes-diseases with the same phenotype but with a different genotype. In the former, the most common congenital heart diseases are aortic coarctation (30%) and bicuspid aortic valve (34%), while in the latter they are pulmonary valvular stenosis (60%), interatrial septal defect (25%) and obstructive or non obstructive hypertrophic cardiomyopathy (17%). We have described two cases, respectively of Noonan's and Turner's syndrome. The prominent features of the first case are the transmission of the syndrome on the male line, since father and son--the latter being our patient--are affected with the same syndrome, and the occurrence of a non obstructive hypertrophic cardiomyopathy involving both the ventricles, a situation not yet described in Noonan's syndrome. A subvalvular membranous aortic stenosis has instead been found in our patient with Turner's syndrome: this cardiac anomaly has never been described within the aforementioned syndrome in medical literature.
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Patients with acute congestive cardiac failure had elevated plasma concentrations of atrial natriuretic peptide (ANP) which fell towards normal levels with successful diuretic therapy. The plasma ANP concentration was closely correlated with the clinical condition of the patients as assessed by serial clinical measurement of the jugular venous pressure and body weight. Plasma ANP concentrations were also raised in patients with a spontaneous acute onset of supraventricular tachycardia but to a lesser extent in patients with chronic tachycardia. Again, successful treatment with d.c. cardioversion returned plasma ANP concentrations towards normal. Induction of atrioventricular re-entrant tachycardia produced an acute and marked rise in plasma ANP concentrations, which rapidly returned to normal when the sinus rhythm was restored. This acute ANP rise probably mediates the known acute natriuretic effect of paroxysmal tachycardia. All the data are consistent with the hypothesis that atrial distension, whatever the cause, releases ANP into plasma.
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Antitumor effect and toxicity of etoposide (VP 16) in combination with cis-diamminedichloroplatinum (DDP) were studied on the in vitro C108 line and its in vivo counterpart, the M1087 line, both deriving from Lewis lung carcinoma. A colony-forming assay was used to assess the in vitro cytotoxicity of each drug and, on the basis of survival curve shape indications, different drug sequences were analyzed in order to find the optimal combination. Tumor growth inhibition, growth delay, metastasis reduction and percentage increase in lifespan were considered as parameters of therapeutic effect. From the present work it can be derived that the VP 16-DDP combination produces a poor antitumour effect against the Lewis lung carcinoma lines, otherwise associated with a highly acute toxicity. The sequence in which VP 16 is given before DDP induces a significant antimetastatic effect together with acceptable toxicity.
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